Research Background

From invertebrates to humans, males and females of a given species display identifiable differences in behaviors, mostly but not exclusively pertaining to sexual and social behaviors, which are crucial to the reproductive success of the animal and the survival of the species. A long-standing and fundamental neurobiological question is ‘how are sex-specific behaviors such as courtship, mating, nursing, and aggression encoded by neural circuits?’ These dimorphic behaviors include a robust set of species-specific fixed action patterns that can be elicited in socially naïve animals, suggesting that the underlying neuronal substrates necessary for their execution are likely to be genetically determined and developmentally programmed.

Surprisingly, with few exceptions, the quest for traces of fundamental differences in male and female mammalian brain structures and circuits that would parallel those of sexual behaviors and peripheral organs has so far uncovered only modest quantitative differences, rather than the clear qualitative differences we expected.

How do sex differences in behavior arise? What are the molecules and neural circuits that govern sexually dimorphic innate behaviors such as mating, aggression and care of the young? How do sensory and social stimuli modulate innate sexually dimorphic responses?

In most mammals, the vomeronasal organ (VNO) is a primary chemosensory organ that detects pheromonal signals in the environment. Pheromones, present in urine and different exocrine gland secretions, provide information about an individual’s social and reproductive status and can elicit innate immediate behavioral responses, along with long-lasting neuroendocrine responses.

Genetic ablation of the gene encoding TRPC2, an ion channel essential for VNO signaling, has provided a robust experimental system to directly investigate the repertoire of VNO-mediated sensory responses and behaviors. It has been shown that the TRPC2 mutant male exhibits profound defects in male-male aggression and in his ability to distinguish between males and females, displaying mating behavior toward males and females with equal frequency.

Recently we discovered that TRPC2-/- females display a loss of sex discrimination and a reduction in female-specific behaviors, which include maternal aggression and lactating behavior. Remarkably, mutant females also adopted a male-typical pattern of mating behaviors including mounting, pelvic thrust, anogenital olfactory investigation, and emission of complex ultrasonic vocalizations.

Our lab employs multidisciplinary techniques including mouse genetics, neurohistology, molecular biology and extensive behavioral methodologies to uncover the neuronal coding of chemosensory-evoked innate behavioral responses that are crucial to the survival of all animal species. What are the neuronal circuits that encode social behaviors? How do genes, hormones and environmental stimuli regulate social interaction and social communication? Is dominant behavior innate or the result of learned behavioral characteristics? What are the causes for attenuated or abnormal social-linked human disorders, such as autism? Autism spectrum disorders (ASD) etiology is thought to involve an interaction between genetic susceptibility, mediated by multiple genes, and possible environmental factors, leading to aberrant neurodevelopment. However, no valid biomarker for the disorder currently exists and it is diagnosed solely by behavioral assessments. The main diagnostic criteria for ASD are the presence of social deficits, communication abnormalities, behavioral rigidity, and ritualistic-repetitive behaviors. In recent years there has been enormous progress in developing genetic mouse strains that can potentially serve as animal models for the basic or preclinical study of ASD.

To better understand the mechanisms which regulate social behavior and social-related neurodevelopemental disorders such as autism, our lab focuses on screening for mouse models of autism, as well as developing automated behavioral paradigms for systematically evaluating autistic-like behavioral phenotype in mouse models .

Key Research Interests

  • Pheromone signaling - perception, processing and sexually dimorphic behavioral function
  • The genetic and neural basis of innate social and reproductive behaviors and the effects of environmental stimuli
  • Characterization of the behavioral phenotyping of mouse models for autism 
  • Evaluating drug treatments and environmental interventions for reversal of autism-like endophenotypes in mouse models